The mode of action of an effective treatment for multiple sclerosis explained in more detail

10 April 2014

Rodent models for autoimmune diseases have shown a poor predictive value for the situation in humans. The lack of knowledge of the background and treatment methods in relation to this type of disease has led to a stagnation in the development of new treatment methods. Monkey models can play a crucial role in solving this knowledge gap.

Some therapies for autoimmune diseases such as multiple sclerosis (MS) are effective whereas others fail. The underlying cause is often unknown. The immune system of rodents only partially resembles that of humans and therefore rodent models can not provide much insight into the reasons for clues success/failure of new treatments. The immune system of monkeys shows much more similarities to that of humans. This provides the opportunity to study in detail the mechanisms behind the (in)effectiveness for new treatment methods for autoimmune diseases. These insights can provide important clues for the development of new treatments, as described in the journal ‘Drug Discovery Today’.

An example of a study on the underlying mechanisms of an effective treatment for MS, has recently been published in ‘The Journal of Immunology’. Treatment with certain antibodies induces removal of a specific type of immune cells, the CD20-positive B-cell, from the body. These antibodies are very effective in the treatment of MS. Why these antibodies have this effect is unknown. In marmoset monkeys, this treatment is also effective against a disease that is similar to MS.

BPRC researchers have now investigated the effect of the antibodies on various components of the immune system. The immune system normally protects the body against pathogens. However, in rare occasions, the immune system is over-active and direct its activity against molecules of the own host. This may lead to auto-immune diseases, such as MS.

The investigators showed that the administration of antibodies directed against the CD20-positive B-cells resulted in an immune system that is less prone to activation. In addition, it was shown that removal of CD20- positive B-cells from an organ of the immune system resulted in the replacement by a different type of immune cell. This cell type has been implicated in the disease but as a result of the treatment, these cells are changed so that migration to other parts of the body is hampered, and therefore can not cause any disease. This knowledge can form the basis for a targeted approach to develop new and improved methods to treat MS.